**7. Plaque haemorrhage**

Haemorrhage is a common feature of unstable carotid atherosclerotic lesions. [68-72] Intraplaque haemorrhage has been associated with the development and growth of the necrotic plaque core, rapid changes in plaque volume, development of plaque instability, and ischaemic neurological events. [73-76]

The origin of plaque haemorrhage is uncertain. It has been suggested that it may occur from fissures within the plaque cap. [76] Alternatively the new blood vessels within the athero‐ sclerotic plaque may represent the first site of morphologic change that leads to intra-plaque haemorrhage; features such as microvessel density and perivascular inflammatory infiltrate have been associated with the presence and quantity of intra-plaque haemorrhage. [55, 77, 78] Carotid Plaque Morphology: Plaque Instability and Correlation with Development of Ischaemic Neurological Events http://dx.doi.org/10.5772/57254 91

**Figure 3.** New blood vessels in a carotid atherosclerotic plaque. (*Ann Vasc Surg* 2008; 22(2): 266–272.)

development and timing of ipsilateral ischaemic or ocular events and presence of ipsilateral cerebral infarction on computer tomography (CT) scanning. [57-62] Microarray gene chip analysis revealed that the presence of newly formed vessels is associated with increased angiogenic gene expression. [63, 64] These new blood vessels are weak and could be respon‐ sible for intraplaque haemorrhage. Moreover, the endothelial lining of these microvessels express high levels of E-Selectin, ICAM-1, and VCAM-1, which indicates that these endothelial cells are in an activated state. Activated endothelial cells act as local site of inflammatory cell recruitment into the atherosclerotic plaque, perpetuating the inflammatory process within the

Haemorrhage is a common feature of unstable carotid atherosclerotic lesions. [68-72] Intraplaque haemorrhage has been associated with the development and growth of the necrotic plaque core, rapid changes in plaque volume, development of plaque instability, and ischaemic

The origin of plaque haemorrhage is uncertain. It has been suggested that it may occur from fissures within the plaque cap. [76] Alternatively the new blood vessels within the athero‐ sclerotic plaque may represent the first site of morphologic change that leads to intra-plaque haemorrhage; features such as microvessel density and perivascular inflammatory infiltrate have been associated with the presence and quantity of intra-plaque haemorrhage. [55, 77, 78]

lesion and contribute to plaque destabilization. [65-69]

**Table 2.** Features of Rupture prone (Unstable) Plaques [40]

**7. Plaque haemorrhage**

**Structural:**

**Cellular:**

**Molecular**

Large Lipid rich core Thin Fibrous Cap

Reduces Collagen content

Local Chronic inflammation

**Increased Neovascularity**

Reduced Smooth muscle cell density Increased number and activity of mast cells Expression of markers of inflammatory activation

Matrix Metalloproteinase Secretion Increased Tissue Factor Expression

Increased macrophage density and activity T Lymphocyte accumulation near site of rupture

90 Carotid Artery Disease - From Bench to Bedside and Beyond

neurological events. [73-76]

There is ample clinical and histological evidence that carotid atherosclerotic plaques with large necrotic lipid core, thin plaque cap or ulceration, dense inflammatory infiltrate, intra-plaque haemorrhage and angiogenesis are vulnerable to rupture and development of ischaemic neurological and ocular events. In vivo identification of these changes within carotid athero‐ sclerotic plaques gives these findings clinical significance in the context of patients with significant carotid atherosclerosis. For over two decades, non-invasive imaging modalities such as duplex ultrasound and magnetic resonance imaging have been in clinical use. They have been used for the measurement of internal carotid artery stenosis. [79-81] These imaging modalities can also be used to study morphological changes associated with plaque instability and development of ischaemic neurological events. [82-85]
